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Synthesis method of 5-(piperazino-1-yl)benzofuryl-2-formamide

A technology of benzofuran and synthetic method, which is applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of low product yield and purity, long synthetic route, etc., and achieve high product yield and purity, simple and convenient production process, and good product quality Effect

Active Publication Date: 2013-03-13
SUZHOU UUGENE BIOPHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] Although the cost of raw materials used in this synthetic method has been reduced, the synthetic route is longer and the yield and purity of the final product are lower

Method used

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  • Synthesis method of 5-(piperazino-1-yl)benzofuryl-2-formamide
  • Synthesis method of 5-(piperazino-1-yl)benzofuryl-2-formamide
  • Synthesis method of 5-(piperazino-1-yl)benzofuryl-2-formamide

Examples

Experimental program
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Effect test

Embodiment 1

[0049] 1) Preparation of 4-(piperazin-1-yl) salicylaldehyde (II)

[0050] At room temperature, add 1000 mL of anhydrous acetonitrile to the reaction flask under the protection of nitrogen, then add 37.25 g of 4-piperazin-1-yl-phenol, MgCl 2 30.1g, 110mL of triethylamine, 31.35g of paraformaldehyde, heat up and reflux for 5 hours, wait for the reaction solution to cool to room temperature, slowly pour the reaction solution into 1L of hydrochloric acid with a concentration of 5%, and mix the liquid with 1L of dichloro Methane was extracted twice, the water phase was adjusted to PH to 8 with 10% NaOH aqueous solution, a large amount of solids were precipitated, filtered with suction, the filter cake was washed twice with a small amount of water to remove inorganic salts, and the filter cake was air-dried at 55~65°C. 37.5 g of a light yellow solid was obtained with a yield of 88% and a purity of 98%.

[0051] 2) Preparation of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate (II...

Embodiment 2

[0056] 1) Preparation of 4-(piperazin-1-yl) salicylaldehyde (II)

[0057] At room temperature, add 900 mL of tetrahydrofuran to the reaction flask under the protection of nitrogen, then add 44.2 g of 4-piperazin-1-yl-phenol, MgCl 2 35.6g, 135mL pyridine, 37.2g paraformaldehyde, heat up and reflux for 4 hours, wait for the reaction solution to cool to room temperature, slowly pour the reaction solution into 1L hydrochloric acid with a concentration of 5%, and extract the mixed liquid with 1L dichloromethane Twice, the water phase was adjusted to PH to 8 with 10% NaOH aqueous solution, a large amount of solids were precipitated, filtered with suction, the filter cake was washed twice with a small amount of water to remove inorganic salts, and the filter cake was air-dried at 55~65°C to obtain 37.8 g of pale yellow solid, yield 86.5%, purity 98.5%.

[0058] 2) Preparation of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate (III)

[0059] At room temperature, add 425 mL of DMF ...

Embodiment 3

[0063] 1) Preparation of 4-(piperazin-1-yl) salicylaldehyde (II)

[0064] At room temperature, add 1000mL of toluene to the reaction flask under the protection of nitrogen, then add 42.5g of 4-piperazin-1-yl-phenol, MgCl 2 33.6g, 165mL of diisopropylethylamine, 35.8g of paraformaldehyde, heat up and reflux for 7 hours, wait for the reaction solution to cool to room temperature, slowly pour the reaction solution into 1L hydrochloric acid with a concentration of 5%, and use the mixed liquid with Extract twice with 1L dichloromethane, adjust the pH of the water phase to 8 with 10% NaOH aqueous solution, precipitate a large amount of solids, filter with suction, wash the filter cake twice with a small amount of water to remove inorganic salts, blow the filter cake at 55~65°C After drying, 37.2 g of a light yellow solid was obtained, with a yield of 75.6% and a purity of 98%.

[0065] 2) Preparation of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate (III)

[0066] At room temper...

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Abstract

The invention relates to a synthesis method of a vilazodone hydrochloride intermediate 5-(piperazino-1-yl)benzofuryl-2-formamide, belonging to the technical field of medicine synthesis. The synthesis method comprises the following steps: reacting a compound disclosed as Formula (I) with polyformaldehyde under reflux for 3-10 hours, carrying out cyclization reaction with ethyl chloroacetate at 80-120 DEG C for 3-24 hours, dissolving in alcohol, introducing ammonia gas, and reacting at 10-80 DEG C under the pressure of 0.1-2.0 Mpa for 3-24 hours to obtain a compound disclosed as Formula (IV), wherein the structural formulae of the Formula (I) and Formula (IV) are disclosed in the specification: when R is H, the compound disclosed as Formula (IV) is the product 5-(piperazino-1-yl)benzofuryl-2-formamide, and when R is a nitrogen protecting group, the protecting group can be removed to obtain the target product 5-(piperazino-1-yl)benzofuryl-2-formamide. The synthesis method has the advantages of low cost, short production procedure, high product yield and purity, and good product quality.

Description

technical field [0001] The invention relates to a synthesis method of a pharmaceutical intermediate, in particular to a synthesis method of vilazodone hydrochloride intermediate 5-(piperazin-1-yl)benzofuran-2-carboxamide, and belongs to the technical field of pharmaceutical synthesis. Background technique [0002] The chemical name of vilazodone hydrochloride is 5-(4-(4-(5-cyano-3-indolyl)butyl)-1-piperazinyl)benzofuran-2-carboxamide hydrochloride, The chemical structural formula is: [0003] [0004] Vilazodone hydrochloride is a new antidepressant drug developed by Clinical Data for the treatment of depression in adults. Compared with the existing clinical antidepressants, the drug has the characteristics of rapid onset of action and no side effects of sexual dysfunction for patients. [0005] Among them, 5-(piperazin-1-yl)benzofuran-2-carboxamide is an important intermediate in the synthesis of vilazodone hydrochloride, using 5-(piperazin-1-yl)benzofuran-2- The synt...

Claims

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Application Information

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IPC IPC(8): C07D307/85
CPCY02P20/55
Inventor 王伸勇宋丰奎王晓俊胡隽恺
Owner SUZHOU UUGENE BIOPHARMA
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